GJB3在携带GJB2单等位基因突变的中国耳聋人群中的突变分析

Sequence analysis of GJB3 in Chinese deafness population who carry one heterozygous GJB2 pathogenic mutation

目的在GJB2病理性单等位基因突变携带者中进行GJB3基因编码区序列分析，探讨GjB2与GJB3双基因模式遗传致聋的可能性。方法对从全国24个省市自治区3323例重度．极重度感音神经性耳聋患者中筛查出的108例携带GJB2病理性单等位基因突变的耳聋患者进行GJB3基因编码区全序列测序，分析测得序列，对所发现突变或变异编码氨基酸的物种进化保守性进行分析，结合听力正常对照人群中GJB3基因编码区测序结果，对考虑为携带GJB3突变及GJB2病理性单等位基因突变的耳聋患者进行家系分析。结果108例携带GJB2病理性单等位基因突变的耳聋患者中共检测到7种GJB3基因变异类型，其中错义突变3种，静止变异4种。5例携带GJB3基因的错义变异（V84I，A194T，N166S），结合对照组检测结果，V84I为中国人群GJB3基因的多态改变，GJB3基因N166S和A194T可能为导致常染色体隐性非综合征性耳聋的的病理性突变。结论GJB3与GJB2可能以双基因模式遗传导致耳聋，其致病机制还待进一步阐明。

Objective To investigate whether GJB3 and GJB2 interaction to produce a deafness phenotype in a digenic mode of inheritance in Chinese deafness population. Methods A series of 108 patients with severe or profound hearing loss carrying one heterozygous GJB2 pathogenic mutation were sequenced for GJB3 coding region, which compared with the data of control group. Results Three GJB3 missense variants including V84I, A194T and N166S, and four GJB3 nonsense mutation were detected. N166S and A194T were considered as pathogenic which cause nonsyndromic autosomal recessive hearing loss and V84I was considered as polymorphisms in Chinese population. The two patients who carried N166S and A194T respectively in one allele also carried GJB2 235delC mutation in other allele, while the other patient who carried A194T in one allele also carried GJB2 299_300delAT mutation in other allele. Conclusions GJB3 and GJB2 might interact to produce deafness in a digenic mode of inheritance, but the point need to be proved in further study.